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@ARTICLE{Ovesen:276822,
      author       = {Ovesen, Peter Lund and Juul-Madsen, Kristian and Telugu,
                      Narasimha S and Schmidt, Vanessa and Frahm, Silke and
                      Radbruch, Helena and Louth, Emma Louise and Korshøj, Anders
                      Rosendal and Heppner, Frank L and Diecke, Sebastian and
                      Kettenmann, Helmut and Willnow, Thomas E},
      title        = {{A}lzheimer's {D}isease {R}isk {G}ene {SORL}1 {P}romotes
                      {R}eceptiveness of {H}uman {M}icroglia to
                      {P}ro-{I}nflammatory {S}timuli.},
      journal      = {Glia},
      volume       = {73},
      number       = {4},
      issn         = {0894-1491},
      address      = {Bognor Regis [u.a.]},
      publisher    = {Wiley-Liss},
      reportid     = {DZNE-2025-00335},
      pages        = {857 - 872},
      year         = {2025},
      abstract     = {Sorting protein-related receptor containing class A repeats
                      (SORLA) is an intracellular trafficking receptor encoded by
                      the Alzheimer's disease (AD) gene SORL1 (sortilin-related
                      receptor 1). Recent findings argue that altered expression
                      in microglia may underlie the genome-wide risk of AD seen
                      with some SORL1 gene variants, however, the functional
                      significance of the receptor in microglia remains poorly
                      explained. Using unbiased omics and targeted functional
                      analyses in iPSC-based human microglia, we identified a
                      crucial role for SORLA in sensitizing microglia to
                      pro-inflammatory stimuli. We show that SORLA acts as a
                      sorting factor for the pattern recognition receptor CD14,
                      directing CD14 exposure on the cell surface and priming
                      microglia to stimulation by pro-inflammatory factors. Loss
                      of SORLA in gene-targeted microglia impairs proper CD14
                      sorting and blunts pro-inflammatory responses. Our studies
                      indicate an important role for SORLA in shaping the
                      inflammatory brain milieu, a biological process important to
                      local immune responses in AD.},
      keywords     = {Humans / Microglia: metabolism / Alzheimer Disease:
                      genetics / Alzheimer Disease: metabolism / Alzheimer
                      Disease: pathology / LDL-Receptor Related Proteins: genetics
                      / LDL-Receptor Related Proteins: metabolism / Membrane
                      Transport Proteins: genetics / Membrane Transport Proteins:
                      metabolism / Lipopolysaccharide Receptors: metabolism /
                      Lipopolysaccharide Receptors: genetics / Induced Pluripotent
                      Stem Cells: metabolism / Inflammation: metabolism /
                      Inflammation: genetics / Alzheimer's disease (Other) / SORLA
                      (Other) / VPS10P domain receptors (Other) / brain
                      inflammation (Other) / microglia (Other) / SORL1 protein,
                      human (NLM Chemicals) / LDL-Receptor Related Proteins (NLM
                      Chemicals) / Membrane Transport Proteins (NLM Chemicals) /
                      Lipopolysaccharide Receptors (NLM Chemicals) / CD14 protein,
                      human (NLM Chemicals)},
      cin          = {AG Heppner},
      ddc          = {610},
      cid          = {I:(DE-2719)1810007},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39688327},
      pmc          = {pmc:PMC11845846},
      doi          = {10.1002/glia.24659},
      url          = {https://pub.dzne.de/record/276822},
}